title: Relative induction of heat shock protein in coronary endothelial cells and cardiomyocytes: implications for myocardial protection.
abstract: OBJECTIVE
  Induction of the 70 kd heat shock protein in the heart is known to exert a protective effect against postischemic mechanical and endothelial dysfunction. However, the exact site of induction and the mechanisms involved remain unknown. The aim of this study was to investigate the relative capacity of endothelial and myocardial cells to express the 70 kd heat shock protein in response to heat stress, as well as their significance.
  
  
  METHODS
  (1) Postischemic recovery of cardiac mechanical and endothelial function was studied in isolated rat hearts with and without endothelial denudation with saponin. (2) Semiquantitative determination of induction of 70 kd heat shock protein by Western immunoblotting was performed in the whole cardiac homogenate, in isolated cardiac myocytes, and in coronary endothelial cells. (3) Immunocytochemistry was used to visualize the distribution of induction of 70 kd heat shock protein in both cell types.
  
  
  RESULTS
  Postischemic recovery (percent preischemic value +/- standard error of the mean) of cardiac output in hearts from heat-stressed animals was significantly improved (66.7 +/- 6.9 vs 44.5 +/- 4.5 in the control group, p < 0.01). In heat-stressed hearts treated with saponin no improvement in the recovery of cardiac output was noted (44.7 +/- 6.9 in heat-stressed hearts vs 38.0 +/- 4.0 in heat-stressed, saponin-treated hearts, p = not significant). Endothelial function (as assessed by the vasodilatory response to the endothelium-dependent vasodilator 5-hydroxytryptamine) improved from 31.0 +/- 5.2 in the control group to 65.8 +/- 7.1 in heat-stressed hearts (p < 0.02 vs control) and dropped to -1.9 +/- 3.8 in heat-stressed hearts treated with saponin. Immunocytochemistry showed that only sections of hearts from heat-treated rats showed a strong specific reaction with heat shock protein antibody. The positive staining was seen in endothelial cells. Induction of 70 kd heat shock protein content in the whole cardiac homogenate from heat-stressed rats as measured by Western immunoblotting was 5.2 +/- 1.9 (vs 0.0 in non-heat-stressed rats, p < 0.0001) and dropped to 0.0 in heat-stressed hearts treated with saponin. The tentative amount of 70 kd heat shock protein was 18.1 +/- 7.8 in isolated endothelial cells from heat-stressed hearts and 2.3 +/- 2.3 in isolated cardiac myocytes (p < 0.01 vs endothelial cells).
  
  
  CONCLUSIONS
  Coronary endothelial cells are the main site of induction of 70 kd heat shock protein in the heart and appear to contribute to the protective effects of heat stress on the recovery of mechanical and endothelial function.
authors.affiliation: Department of Cardiothoracic Surgery, National Heart and Lung Institute, Harefield Hospital, Harefield, Middlesex, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Amrani
authors.forename: N
authors.initials: N
authors.lastname: Latif
authors.forename: K
authors.initials: K
authors.lastname: Morrison
authors.forename: C C
authors.initials: CC
authors.lastname: Gray
authors.forename: J
authors.initials: J
authors.lastname: Jayakumar
authors.forename: J
authors.initials: J
authors.lastname: Corbett
authors.forename: A T
authors.initials: AT
authors.lastname: Goodwin
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunn
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006324:Heart Arrest, Induced; D006358:Hot Temperature; D007150:Immunohistochemistry; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D012503:Saponins